MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors

NCT ID: NCT02444884

Last Updated: 2016-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2011-12-31

Brief Summary

RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors

Detailed Description

1.1 Primary Aims 1.1.1 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally once daily for 7 days every 21 days to children with refractory solid tumors. 1.1.2 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally twice daily for 7 days every 21 days to children with refractory solid tumors. 1.1.3 To define and describe the toxicities of MLN8237 administered on this schedule.

1.1.4 To characterize the pharmacokinetics of MLN8237 in children with refractory cancer.

1.2 Secondary Aims 1.2.1 To preliminarily define the antitumor activity of MLN8237 within the confines of a Phase I study. 1.2.2 To obtain initial Phase II efficacy data on the anti-tumor activity of MLN8237 in children with relapsed-refractory neuroblastoma using the once daily dosing schedule. 1.2.3 To explore the relationship between polymorphic variations in the UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237.

1.2.4 To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis. 1.2.5 To preliminarily examine the relationsh

Conditions

Unspecified Childhood Solid Tumor, Excluding CNS; Neuroblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stratum A1

Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7

Group Type: EXPERIMENTAL

MLN8237

Intervention Type: DRUG

Stratum A2

MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7

Group Type: EXPERIMENTAL

MLN8237

Intervention Type: DRUG

Stratum B

Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7

Group Type: EXPERIMENTAL

MLN8237

Intervention Type: DRUG

Interventions

MLN8237

Intervention Type: DRUG

Other Intervention Names

Alisertib

Eligibility Criteria

Inclusion Criteria

• Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetaprotein or beta-HCG.
• Performance Level: Karnofsky >/= 50% for patients > 16 years of age and Lansky

>/= 50 for patients </=16 years of age

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Adequate Bone Marrow Function Defined as:

a. For patients with solid tumors:

• Peripheral absolute neutrophil count (ANC) >/= 1000/microLiter
• Platelet count >/= 100,000/microLiter (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
• Hemoglobin >/= 8.0 g/dL (may receive RBC transfusions)
• Creatinine clearance or radioisotope GFR >/= 70ml/min/1.73 m2
• Bilirubin (sum of conjugated + unconjugated) </= 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) </= 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L.
• Serum albumin >/= 2 g/dL.

Exclusion Criteria

• Pregnant or breast-feeding women will not be entered on this study
• Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment.
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible.
• Patients who are currently receiving another investigational drug are not eligible.
• Patients who are currently receiving other anticancer agents, digoxin, cyclosporine, tacrolimus or sirolimus, use of daily benzodiazepines are not eligible
• Patients who have an uncontrolled infection are not eligible.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Zhou X, Mould DR, Yuan Y, Fox E, Greengard E, Faller DV, Venkatakrishnan K. Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies. J Clin Pharmacol. 2022 Feb;62(2):206-219. doi: 10.1002/jcph.1958. Epub 2022 Jan 15.

Reference Type: DERIVED

PMID: 34435684 (View on PubMed)

Other Identifiers

ADVL0812

Identifier Type: -

Identifier Source: org_study_id